一种基因组调节元件,指导免疫特异AP-1-IRF复合体的组装和功能
Elke Glasmacher1, Smita Agrawal, Abraham B Chang
1Department of Discovery Immunology, Genentech, Incorporated, South San Francisco, CA 94080, USA.
Science (New York, N.Y.)
|September 18, 2012
概括
干扰素调节因子4 (IRF4) 和BATF共同与调节元素结合,推动T辅助17细胞的分化. 这种机制将各种免疫细胞的免疫信号整合在一起.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 干扰素调节因子 (IRF),如IRF4和IRF8,对于免疫细胞的分化至关重要.
- IRF通常与Ets因子结合cis调节元件,但它们在缺乏特定Ets合作伙伴的T细胞中的向性尚不清楚.
研究的目的:
- 阐明IRF4针对T细胞中的基因,特别是T辅助细胞17 (T) 的机制.
- 为了确定参与T(H) 17细胞中IRF4-介导基因调节的DNA动机和蛋白质合作伙伴.
主要方法:
- 染色体免疫沉测序 (ChIP-seq) 在T(H) 17细胞上进行.
- 分析的重点是确定由IRF4和其他转录因子共同结合的DNA序列.
主要成果:
- 发现IRF4在T(H) 17细胞中准激活蛋白1 (AP-1) -IRF复合元件 (AICE).
- 一个AP-1家族成员的BATF被确定为AICEs的IRF4的关键联合约束合作伙伴.
- IRF4和BATF通过合作方式与各种AICE结合,促进基因激活和T(H) 17分化.
结论:
- AICE 图案是 IRF4 和 BATF 结合的关键基因组调节元素.
- 在AICE中这种IRF4-BATF相互作用对于T(H) 17细胞分化至关重要,并且也用于其他免疫细胞类型.
- 这些发现揭示了通过特定的转录因子-DNA元素相互作用整合免疫调节信号的保存机制.
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